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Korean J Transplant 2021; 35(3): 168-176

Published online September 30, 2021

https://doi.org/10.4285/kjt.21.0012

© The Korean Society for Transplantation

Efficacy and safety of a switch from twice-daily tacrolimus to once-daily generic tacrolimus in stable liver transplant patients

Jong Man Kim1 , Pyoung-Jae Park2,3 , Geun Hong4 , Dong Jin Joo5 , Kwan Woo Kim6 , Je Ho Ryu7 , Young Seok Han8 , Jai Young Cho9 , Gi-Won Song10 , Bong-Wan Kim11 , Dong-Sik Kim2 , Seong Hoon Kim12 , Sang Tae Choi13 , Young Kyoung You14 , Kyung-Suk Suh15 , Yang-Won Na16 , Koo Jeong Kang17 , Jae-Won Joh1

1Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Department of Surgery, Korea University College of Medicine, Seoul, Korea
3Department of Surgery, Korea University Guro Hospital, Seoul, Korea
4Department of Surgery, Ewha Woman's University School of Medicine, Seoul, Korea
5Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
6Department of Surgery, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
7Department of Surgery, Pusan National University College of Medicine, Busan, Korea
8 Department of Surgery, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
9 Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
10Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
11 Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Ajou University School of Medicine, Suwon, Korea
12Center for Liver Cancer, National Cancer Center, Goyang, Korea
13 Department of Surgery, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
14Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Korea
15Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
16Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
17 Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Korea

Correspondence to: Jae-Won Joh
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, 06351 Seoul, Korea
Tel: +82-2-3410-3466
Fax: +82-2-3410-0040
E-mail: jw.joh@samsung.com

Received: May 24, 2021; Revised: August 27, 2021; Accepted: September 9, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Once-daily tacrolimus reduces non-compliance relative to twice-daily tacrolimus. However, little is known about the safety and efficacy of conversion from twice-daily tacrolimus to generic once-daily tacrolimus in liver transplantation (LT). Herein, we investigated the efficacy and safety of a switch from twice-daily tacrolimus to generic once-daily tacrolimus in patients with stable liver graft function.
Methods: This prospective, multicenter, open-label, single-arm study was conducted in 17 medical centers for 1 year from July 2019 to July 2020 (NCT04069065). Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR) for 24 weeks after conversion. Secondary endpoints were graft failure, patient death, and adverse events (AEs).
Results: Of 151 screened LT patients, 144 patients were enrolled. BPAR, graft failure, and patient death did not occur in this patient population. There were no statistical differences in blood tests, liver function tests, or biochemical tests between visits in any of the patients. Median tacrolimus trough level decreased abruptly from 4.7 ng/mL to 3.2 ng/mL after generic once-daily tacrolimus conversion, but median tacrolimus dose increased due to low tacrolimus trough level. Ninety-two adverse events occurred in 54 patients. Liver enzyme levels increased in seven patients (4.9%) after the switch to generic once-daily tacrolimus, but the liver function tests of these patients normalized thereafter. There were three cases of severe AEs not related to investigational drug.
Conclusions: Present study suggests that conversion from twice-daily tacrolimus to generic once-daily tacrolimus is effective and safe in stable LT patients.

Keywords: Tacrolimus, Liver transplantation, Therapeutic equivalence, Immunosuppression

HIGHLIGHTS
  • Biopsy-proven acute rejection, graft failure, and patient death did not occur after conversion to generic once-daily tacrolimus in stable liver transplant patients.

  • Therefore, present study suggests that switch from twice-daily tacrolimus to generic once-daily tacrolimus is effective and safe.